title: Infiltrating Foxp3(+) regulatory T cells from spontaneously tolerant kidney allografts demonstrate donor-specific tolerance.
abstract: Foxp3(+) regulatory T cells (Tregs) have an essential role in immune and allograft tolerance. However, in both kidney and liver transplantation in humans, FOXP3(+) Tregs have been associated with clinical rejection. Therefore, the role and function of graft infiltrating Tregs have been of great interest. In the studies outlined, we demonstrated that Foxp3(+) Tregs were expanded in tolerant kidney allografts and in draining lymph nodes in the DBA/2 (H-2(d) ) to C57BL/6 (H-2(b) ) mouse spontaneous kidney allograft tolerance model. Kidney allograft tolerance was abrogated after deletion of Foxp3(+) Tregs in DEpletion of REGulatory T cells (DEREG) mice. Kidney allograft infiltrating Foxp3(+) Tregs (K-Tregs) expressed elevated levels of TGF-β, IL-10, interferon gamma (IFN-γ), the transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) and chemokine receptor 3 (Cxcr3). These K-Tregs had the capacity to transfer dominant tolerance and demonstrate donor alloantigen-specific tolerance to skin allografts. This study demonstrated the crucial role, potency and specificity of graft infiltrating Foxp3(+) Tregs in the maintenance of spontaneously induced kidney allograft tolerance.
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead, University of Sydney, Westmead, NSW, Australia; Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Hu
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: G Y
authors.initials: GY
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: Y M
authors.initials: YM
authors.lastname: Wang
authors.forename: M A
authors.initials: MA
authors.lastname: Fernandez
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: W J
authors.initials: WJ
authors.lastname: Hawthorne
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Connell
authors.forename: T
authors.initials: T
authors.lastname: Sparwasser
authors.forename: G A
authors.initials: GA
authors.lastname: Bishop
authors.forename: A F
authors.initials: AF
authors.lastname: Sharland
authors.forename: S I
authors.initials: SI
authors.lastname: Alexander
mesh_terms: D064591:Allografts; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000502:physiology*; D017930:Genes, Reporter; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D018836:Inflammation Mediators; D016030:Kidney Transplantation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014019:Tissue Donors; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators
keywords: DEREG mice; Depletion of Foxp3+ Tregs; donor alloantigen-specific tolerance; kidney allograft infiltrating Foxp3+ Tregs; spontaneous kidney allograft tolerance